Output Catalog
ASAP is committed to accelerating the pace of discovery and informing a path to a cure for Parkinson’s disease through collaboration, research-enabling resources, and data sharing. We’ve created this catalog to showcase the research outputs and tools developed by ASAP-funded programs.
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Spermidine suppresses glial inflammation and parkinsonian abnormalities in ATP13A2 deficiency
Pathogenic variants in ATP13A2 cause Kufor-Rakeb syndrome & early-onset parkinsonism. Spermidine supplementation rescues symptoms by counteracting microglia dysfunction & improving neuronal integrity.
NERINE reveals rare variant associations in gene networks across phenotypes and implicates an SNCA-PRL-LRRK2 subnetwork in Parkinson’s disease
NERINE is a rare variant association test that links rare genetic variation with gene network topology to improve discovery power in complex diseases. NERINE implicates an α-synuclein/prolactin stress-response in Parkinson’s disease.
Regulation of the proteasome 20S core particle by the Parkinsonism-associated Proteins FBXO7 and PI31
Genetic forms of PD are associated with variants in FBXO7 and PI31. Combining biochemical and structural approaches, we describe the proteasome interaction of these proteins and map disease variants to disruption of proteasome interaction.
Fluorescence-Gated Flow Cytometry Approach for Measuring Lipid Flippase Activity in Mammalian Cells
P4-ATPase lipid flippases create lipid asymmetry in cells. A new strategy using NBD-lipid uptake assays improves sensitivity and analysis of ATP11C function. This method enhances studying regulatory interactions in mammalian cells.
Structural remodeling of the mitochondrial protein biogenesis machinery under proteostatic stress
Cryo-ET showed protein aggregates, altered cristae, and reduced ribosome complexes in stressed mitochondria. Mitochondrial Hsp60 undergoes conformational changes to aid in protein folding, shedding light on mitochondrial proteostasis mechanisms.
Single cell eQTL mapping reveals convergent glial–neuronal risk architecture in Parkinson’s disease
Population-scale, disease-context aware meta single-nucleus eQTLs mapping (N = 1,197) in nine cell types from cortex and substantia nigra identifies 125 risk genes and cell types for PD GWAS signals.
Behavioral screening defines the molecular Parkinsonism-related subgroups in Drosophila
We created a new collection of 24 genetically well-controlled Drosophila models of familial forms of parkinsonism. Using unbiased behavioral screening and machine learning we identified three clusters of mutants that converge.
Integrating Long-Read Structural Variant Analysis with single-nucleus RNA-seq to Elucidate Gene Expression Effects in Disease
Long-read sequencing in PD brain samples identified 74,552 structural variants. Integrating RNA sequencing data revealed SVs near PD-related genes impacting cell type-specific expression, highlighting the importance of SVs in complex diseases.
Modeling cis-regulatory variation in human brain enhancers across a large Parkinson’s Disease cohort
GWAS have linked more than hundred non-coding genomic loci to Parkinson’s disease (PD) risk. Here, we establish a unique resource and new sequence modeling strategies to interpret functional non-coding variation in the human brain.
ATP13A2 Loss of Function-Driven Polyamine Dysregulation Induces SAM Depletion and Epigenetic Astrocyte Toxicity
Loss of ATP13A2 function leads to lysosomal polyamine sequestration, depleting cytosolic polyamines in astrocytes. This triggers compensatory polyamine biosynthesis, diverting SAM from DNA methylation and promoting neuroinflammation.
Selective loss of Primary Cilia and Neurotrophic Signaling in G51D α-Synuclein Mice Highlights a Common Pathway to Parkinson’s Disease
G51D α-synuclein mice mimic disease symptoms, showing cilia loss in specific neurons and impaired neurotrophic signaling, contributing to disease progression. This highlights the role of ciliary dysfunction in Parkinson’s.
A RAB7A Phosphoswitch Coordinates Rubicon Homology Protein Regulation of PINK1/Parkin-Dependent Mitophagy
Published: Structural and functional data support a model in which the TBK1-dependent phosphorylation of RAB7A serves as a switch, promoting mitophagy by relieving Rubicon inhibition and favoring Pacer activation. View original preprint.
A data-driven single-cell and spatial transcriptomic map of the human prefrontal cortex
A data-driven molecular map of the DLPFC reveals distinct spatial domains and cell populations, offering insights into neuropsychiatric disorders. The study provides a roadmap for implementing spatial clustering approaches in the human brain.
Evaluation Of The Rims2 Locus As A Risk Locus For Parkinson’s Disease Dementia
Liu et al. found RIMS2 locus linked to dementia in Parkinson's disease. Our study with 2536 individuals found no association with RIMS2 or other loci. More research is needed to uncover biological factors influencing Parkinson's dementia.
Nicotine-Mediated Rescue of α-Synuclein Toxicity Requires Synaptic Vesicle Glycoprotein 2 in Drosophila
Background: Parkinson’s disease (PD) is characterized by α-synuclein aggregation and loss of dopamine neurons. Risk of PD arises due to a combination of genetic and environmental factors, which may interact, termed gene-environment (G×E)…
